From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies

Ottaiano, Alessandro; Ianniello, Monica; Santorsola, Mariachiara; Ruggiero, Raffaella; Sirica, Roberto; Sabbatino, Francesco; Perri, Francesco; Cascella, Marco; Di Marzo, Massimiliano; Berretta, Massimiliano; Caraglia, Michele; Nasti, Guglielmo; Savarese, Giovanni

doi:10.3390/biology12091183

Cited by 9 publications

(6 citation statements)

References 138 publications

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“…This explains the lower effectiveness of targeted drugs in patients with known metastases and has important clinical significance in targeted therapy. On the other hand, Ottaiano et al [21] stated that tumor heterogeneity can be divided into temporal and spatial heterogeneity. Temporal heterogeneity occurs over time within a single tumor or between different tumors in the same patient.…”

Section: Discussionmentioning

confidence: 99%

Tumor heterogeneity and its impact on sotorasib response in a patient with non-small cell lung cancer

Nalewaj,

Chmielewska,

Krawczyk

et al. 2024

Oncol Clin Pract

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Mutations in the Kirsten rat sarcoma virus (KRAS) gene are the most common mutations in NSCLC, and they occur in 25-40% of patients with lung adenocarcinoma. Sotorasib, a selective KRAS inhibitor, is an anticancer drug used in NSCLC patients with a G12C mutation in the KRAS gene. In previously treated patients, this therapy was safer and more effective than docetaxel chemotherapy. Heterogeneity refers to differences between tumor cells within a single tumor as well as in primary and metastatic lesions. It may influence the response to targeted therapies and the development of acquired resistance to these therapies. It is assumed that sotorasib efficacy is lower in patients with known tumor molecular heterogeneity, which may be common in patients exposed to tobacco smoke. This case report presents a 63-year-old woman with advanced NSCLC and a confirmed G12C mutation in the KRAS gene detected with the real-time PCR technique. A later next-generation sequencing (NGS) examination did not show the presence of this mutation. However, the NGS study was performed on material from a different metastatic lesion. The negative NGS result from this material was confirmed by the real-time PCR technique. The patient had a short-term benefit from first-line chemotherapy and second-line nivolumab immunotherapy (disease stabilization). Due to progression (progression of measurable lesions and new metastases to the CNS), the patient received brain radiotherapy and then sotorasib in the third line of treatment. However, the effectiveness of KRAS inhibition was limited. Regression of the lesion with a detected mutation in the KRAS gene and progression of lesions without this mutation were observed. Sotorasib therapy was terminated. The woman died two years after diagnosis, not benefiting from subsequent lines of therapy. NSCLC heterogeneity (presence of mutations in only some clones of cancer cells) may be responsible for primary and acquired resistance to molecularly targeted therapies, including KRAS inhibitors.

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Section: Discussionmentioning

confidence: 99%

Tumor heterogeneity and its impact on sotorasib response in a patient with non-small cell lung cancer

Nalewaj,

Chmielewska,

Krawczyk

et al. 2024

Oncol Clin Pract

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“…Exclusion criteria encompassed: (1) Other study types (2) Studies involving pediatric populations (age below 18 years); (3) Studies exclusively focused on patients with tumors other than lung primary tumors; (4) Studies not utilizing radiomics analysis for predicting Ki-67 index status; (5) Studies employing imaging modalities other than CT scan for radiomics analysis; (6) Studies lacking relevant diagnostic performance metrics or outcomes related to Ki-67 index categories.…”

Section: Methodsmentioning

confidence: 99%

“…Radiomics, a novel medical imaging method, may improve lung cancer diagnosis by extracting quantitative data from common imaging modalities such as computed tomography (CT) scans and magnetic resonance imaging (MRIs) (4). This approach provides novel insights into tumor heterogeneity and behavior through the automated extraction and analysis of detailed tumor features such as texture and shape (5). Building upon non-invasive and repeatable imaging modalities, radiomics provides insights into lung cancer progression and therapy response (6).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Performance of Radiomics in Prediction of Ki-67 Index Status in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Shahidi,

Hassannejad,

Baradaran

et al. 2024

Preprint

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Background: Lung cancer is a global health concern, in part due to its high prevalence and invasiveness. The Ki-67 index, indicating cellular proliferation, is pivotal for assessing lung cancer aggressiveness. Radiomics is the inference of quantifiable data features from medical images through algorithms and may offer insights into tumor behavior. Here, we perform a systematic review and meta-analysis to assess the performance of radiomics for predicting Ki-67 status in Non-small Cell Lung Cancer (NSCLC) on CT scan. Methods and materials: A comprehensive search of the current literature was conducted using relevant keywords in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception to November 16, 2023. Original studies discussing the performance of CT-based radiomics for predicting Ki-67 status in NSCLC cohorts were included. The quality assessment involved quality assessment of diagnostic accuracy studies (QUADAS-2) and radiomics quality score (RQS). Quantitative meta-analysis, using R, assessed pooled sensitivity and specificity in NSCLC cohorts. Results: We identified 10 studies that met the inclusion criteria, involving 2279 participants, with 9 of these studies included in quantitative meta-analysis. The overall quality of the included studies was moderate to high based on QUADAS-2 and RQS assessment. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC training cohorts were 0.78 (95% CI [0.73; 0.83]) and 0.76 (95% CI [0.70; 0.82]), respectively. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC validation cohorts were 0.79 (95% CI [0.73; 0.84]) and 0.69 (95% CI [0.61; 0.76]), respectively. Substantial heterogeneity was noted in the pooled sensitivity and specificity of training cohorts and the pooled specificity of validation cohorts (I2 > 40%). It was identified that utilizing ITK-SNAP as a segmentation software contributed to a significantly higher pooled sensitivity. Conclusion: This meta-analysis indicates promising diagnostic accuracy of radiomics in predicting Ki-67 in NSCLC. The study underscores radiomics' potential in personalized lung cancer management, advocating for prospective studies with standardized methodologies and larger samples. Keywords: Lung cancer, Ki-67 index, radiomics, CT scan

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“…They are complex due to the presence of numerous interacting components; dynamic because both the components and their interactions can undergo changes over time; and open because the tumor can freely communicate with surrounding and distant host tissue. Significant intratumor variations frequently occur ( 86 ). Tumor blood vessel development and vascular network diversity play a crucial role in tumor progression and spread into secondary metastatic foci ( 85 ).…”

Section: Cc-rcc Associated Vasculogenesismentioning

confidence: 99%

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

Cosma,

Fenesan,

Nesiu

et al. 2024

Front. Oncol.

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Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney’s blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

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From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies

Cited by 9 publications

References 138 publications

Tumor heterogeneity and its impact on sotorasib response in a patient with non-small cell lung cancer

Tumor heterogeneity and its impact on sotorasib response in a patient with non-small cell lung cancer

Diagnostic Performance of Radiomics in Prediction of Ki-67 Index Status in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

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